Dementia results from a wide variety of distinctive pathological processes. The most common pathological processes causing dementia are AD, cerebral amyloid angiopathy (CM) and prion-mediated diseases (see, e.g., Haan et al., Clin. Neurol. Neurosurg. 1990, 92(4):305-310; Glenner et al., J. Neurol. Sci. 1989, 94:1-28). AD is a progressive, neurodegenerative disorder characterized by memory impairment and cognitive dysfunction. AD affects nearly half of all people past the age of 85, the most rapidly growing portion of the United States population. As such, the number of AD patients in the United States is expected to increase from about 4 million to about 14 million by 2050.
Aminodihydrothiazine or thioamidine compounds are described in WO 2010/038686 as useful inhibitors of the β-secretase enzyme. Described therein are also certain compounds that are intermediates to the aminodihydrothiazine compounds. Surprisingly, Applicants determined that at least some of these intermediates are brain-penetrable BACE inhibitors and as such would be expected to be BACE inhibitors and modulators for the treatment of AD and other neurodegenerative diseases (see Olsen et al., Ann. Rep. Med. Chem. 2007, 42:27-47). Accordingly, the present invention is directed to the use of these compounds in the treatment of neurodegenerative diseases, including AD. The invention is also directed to novel thioamidine compounds and their use in the treatment of neurodegenerative diseases, including AD.